The chief manifestation of osteoporosis is the occurrence of fractures. Most osteoporotic fractures occur at skeletal locations rich in trabecular bone. Prevailing among these are the vertebrae, wrist and proximal femur. Hip fractures are the most debilitating among osteoporotic fractures in terms of morbidity and mortality. There is now strong evidence that the loss of bone mass is accompanied by a decline in the trabecular bone net- work's structural integrity. The impaired mechanical competence secondary to gonadal steroid depletion is caused by topological changes in the bone's architectural make-up, chief among which is fenestration of tra becular plates resulting in their conversion to rods and the latter's eventual disruption. Complementing antire- sorptive treatment, new therapies have recently become available to treat the devastating consequences of severe bone loss with bone-forming (i.e. anabolic) drugs. It is not clear, however, whether such therapies are, in fact, able to reverse the disintegration of the trabecular network, and to what extent the structural changes differ from those induced by antiresorptive treatment. In this project we propose to develop novel micro-MRI-based technology suitable to quantify the structural and mechanical consequences of various forms of treatment of patients with metabolic bone disease. We aim to apply this methodology to patients who are at high risk of fracture and who are treated either with 1-34 parathyroid hormone or alendronate. The overall hypothesis is that the new methodology will provide detailed insight into the structural manifestations of trabecular bone subjected to short-term drug treatment. The project will consist of six specific aims involving the development, integration and evaluation of new methods involving data acquisition and reconstruction, motion correction, cryogenic RF coil technology, image processing and analysis, as well as image-based finite-element modeling of bone mechanical competence. We plan to address these goals in partnership with two external collaborators through subcontracts (Dr. Jarek Wosik, Department of Electrical Engineering, Texas Center for Superconductivity, University of Houston, and Dr. Edward Quo, Department of Biomedical Engineering, Columbia University). Already established Penn-internal partnerships with Dr. Charles Epstein (Department of Mathematics) and Dr. Peter Snyder (Department of Medicine, Division of Endocrinology) will be further expanded and strengthened.